[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06915753":3,"trial-entities:NCT06915753":266,"trial-summary:NCT06915753":272},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":33,"study_type":47,"primary_purpose":48,"phases":49,"enrollment_info":51,"interventions":54,"primary_outcomes":63,"secondary_outcomes":76,"sex":106,"minimum_age":107,"maximum_age":108,"healthy_volunteers":15,"eligibility_criteria":109,"std_ages":145,"locations":148,"central_contacts":254,"overall_officials":260,"references":264,"see_also_links":265},"NCT06915753","TYR430-101","Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF\u002FFGFR Pathway Aberrations","A Multicenter, Open-label, First-in-Human Study of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF\u002FFGFR Pathway Aberrations","RECRUITING","2028-09","2026-07","2026-07-29","2025-04-24","Tyra Biosciences, Inc","INDUSTRY",false,"A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF\u002FFGFR pathway aberrations, including locally advanced\u002Fmetastatic hepatocellular carcinoma and other advanced solid tumors.","This is an open-label, multi-center, first-in-human, Phase 1 global study of TYRA-430, a first-in-class, selective, reversible fibroblast growth factor receptor (FGFR) 4 and 3 inhibitor, in locally advanced\u002Fmetastatic hepatocellular carcinoma and other advanced solid tumors that contain FGF\u002FFGFR pathway aberrations.",[19,20,21,22,23,24,25,26,27,28,29,30,31,32],"Metastatic Hepatocellular Carcinoma","Solid Tumors","Solid Tumor, Adult","FGFR Gene Amplification","FGFR Gene Alterations","FGFR3 Gene Alteration","FGFR3 Gene Mutation","Advanced Solid Tumors","FGFR4 Gene Mutation","FGFR4 Gene Fusions","FGF19 Gene Amplification","FGF19 Gene Overexpression","FGFR3 Gene Fusions","Locally Advanced Unresectable Hepatocellular Carcinoma",[34,35,36,37,38,39,40,41,42,43,44,45,46],"Hepatocellular Carcinoma","metastatic cancer","solid tumors","FGF19 gene amplifications","FGFR4 gene alterations","FGFR3 gene alterations","FGF19 gene alterations","FGFR4 gene mutations","FGFR4 gene fusions","FGFR3 gene mutations","FGFR3 gene fusions","FGF19 gene overexpression","locally advanced unresectable cancer","INTERVENTIONAL","TREATMENT",[50],"PHASE1",{"count":52,"type":53},100,"ESTIMATED",[55],{"type":56,"name":57,"description":58,"armGroupLabels":59},"DRUG","TYRA-430","Oral TYRA-430 given daily.",[60,61,62],"Part A - Dose Escalation","Part B - Cohort 1 Dose Expansion","Part B - Cohort 2 Dose Expansion",[64,68,72],{"measure":65,"description":66,"timeFrame":67},"Maximum tolerated dose (MTD)","MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle","Up to 1 year",{"measure":69,"description":70,"timeFrame":71},"Rate and severity of adverse events of TYRA-430 as monotherapy","Number of participants with TEAEs as assessed by CTCAE, v5.0","First dose of study drug through 28 days after the last dose of study drug",{"measure":73,"description":74,"timeFrame":75},"Recommended Phase 2 dose(s) of TYRA-430","To determine recommended Phase 2 dose(s) of TYRA-430","Up to 2 years",[77,79,81,83,85,87,89,91,93,97,100,103],{"measure":78,"timeFrame":75},"Cmax",{"measure":80,"timeFrame":75},"Tmax",{"measure":82,"timeFrame":75},"AUC0-last",{"measure":84,"timeFrame":75},"AUCTau",{"measure":86,"timeFrame":75},"AUC0-∞",{"measure":88,"timeFrame":75},"Vd\u002FF",{"measure":90,"timeFrame":75},"CL\u002FF",{"measure":92,"timeFrame":75},"t1\u002F2",{"measure":94,"description":95,"timeFrame":96},"Overall Response Rate (ORR)","The proportion of patients who experience a best response of confirmed CR or PR per RECIST 1.1","Up to 3.5 years",{"measure":98,"description":99,"timeFrame":96},"Duration of Response (DOR)","Time from first investigator-assessed response to radiographic disease progression or death.",{"measure":101,"description":102,"timeFrame":96},"Disease Control Rate (DCR)","Best response of CR, PR, or SD per RECIST v1.1 \\> 12 months.",{"measure":104,"description":105,"timeFrame":96},"Time to Response (TTR)","The median time from the start of therapy to first response in confirmed responders.","ALL","18 Years",null,{"inclusion":110,"exclusion":128,"raw_text":144},[111,112,113,114,115,116,117,118,119,120,121,122,118,119,123,124,125,126,127,124],"Age ≥ 18 years","Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.","Adequate end organ function.","Ability to swallow oral formulations.","Ability to understand and willingness to sign the ICF.","Histologically confirmed locally advanced unresectable\u002Fmetastatic HCC or histologically confirmed advanced solid tumor with documented FGF\u002FFGFR pathway alterations","For participants with histologically confirmed locally advanced or metastatic HCC:","Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.","Child-Pugh Score class A","Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.","Agree to provide archival tumor tissue no older than 2 years from the time of enrollment, if available. If an archived specimen is not available, a biopsy is not required.","Histologically confirmed locally advanced\u002Fmetastatic HCC who have previously received standard of care.","Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen obtained ≤2 years prior to screening for submission to sponsor-designated central laboratory for FGF19 IHC testing.","At least 1 measurable lesion by RECIST v1.1.","Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.","Must have an eligible activating gain-of-function alteration in the FGFR3 or FGFR4 gene, or focal amplifications of FGF19","Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.",[129,130,131,132,133,134,135,136,137,138,139,140,141,142,143],"Have disease that is suitable for local therapy administered with curative intent.","Have not recovered from reversible toxicity of prior anticancer therapy to \\\u003C Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).","Have received the following anticancer therapy:","Participant discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥ Grade 3 or any Grade 4 toxicity according to CTCAE v5.0.","Has a serum phosphorus level \\> upper limit of normal (ULN) during screening that remains \\>ULN despite medical management.","History of or current uncontrolled cardiovascular disease.","Active, symptomatic, or untreated brain metastases.","Have a diagnosis of primary CNS malignancies.","Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.","Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.","Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.","Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.","Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.","Histologically confirmed locally advanced\u002Fmetastatic HCC.","Histologically confirmed urothelial cancer.","Key Inclusion Criteria:\n\nAll Patients:\n\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.\n* Adequate end organ function.\n* Ability to swallow oral formulations.\n* Ability to understand and willingness to sign the ICF.\n\nPart A:\n\n* Histologically confirmed locally advanced unresectable\u002Fmetastatic HCC or histologically confirmed advanced solid tumor with documented FGF\u002FFGFR pathway alterations\n* For participants with histologically confirmed locally advanced or metastatic HCC:\n\n  * Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.\n  * Child-Pugh Score class A\n* Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.\n* Agree to provide archival tumor tissue no older than 2 years from the time of enrollment, if available. If an archived specimen is not available, a biopsy is not required.\n\nPart B, Cohort 1:\n\n* Histologically confirmed locally advanced\u002Fmetastatic HCC who have previously received standard of care.\n* Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.\n* Child-Pugh Score class A\n* Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen obtained ≤2 years prior to screening for submission to sponsor-designated central laboratory for FGF19 IHC testing.\n* At least 1 measurable lesion by RECIST v1.1.\n\nPart B, Cohort 2:\n\n* Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.\n* Must have an eligible activating gain-of-function alteration in the FGFR3 or FGFR4 gene, or focal amplifications of FGF19\n* Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.\n* At least 1 measurable lesion by RECIST v1.1.\n\nKey Exclusion Criteria:\n\nAll Patients:\n\n* Have disease that is suitable for local therapy administered with curative intent.\n* Have not recovered from reversible toxicity of prior anticancer therapy to \\\u003C Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).\n* Have received the following anticancer therapy:\n\n  1. Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug.\n  2. A TKI \\\u003C 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430.\n  3. Other systemic therapy not listed above \\\u003C 14 days prior to the first dose of the study drug.\n* Participant discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥ Grade 3 or any Grade 4 toxicity according to CTCAE v5.0.\n* Has a serum phosphorus level \\> upper limit of normal (ULN) during screening that remains \\>ULN despite medical management.\n* History of or current uncontrolled cardiovascular disease.\n* Active, symptomatic, or untreated brain metastases.\n* Have a diagnosis of primary CNS malignancies.\n* Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.\n* Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.\n* Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.\n\nPart B, Cohort 1:\n\n* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.\n* Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.\n\nPart B, Cohort 2:\n\n* Histologically confirmed locally advanced\u002Fmetastatic HCC.\n* Histologically confirmed urothelial cancer.",[146,147],"ADULT","OLDER_ADULT",[149,158,165,172,180,188,196,204,211,219,228,235,238,241,244,251],{"facility":150,"status":8,"city":151,"state":152,"zip":153,"country":154,"geoPoint":155},"USC Norris Comprehensive Cancer Center","Los Angeles","California","90033","United States",{"lat":156,"lon":157},34.05223,-118.24368,{"facility":159,"status":8,"city":160,"state":152,"zip":161,"country":154,"geoPoint":162},"UCSF Medical Center at Mount Zion","San Francisco","94158",{"lat":163,"lon":164},37.77493,-122.41942,{"facility":166,"status":8,"city":167,"state":152,"zip":168,"country":154,"geoPoint":169},"Stanford Cancer Institute","Stanford","94305",{"lat":170,"lon":171},37.42411,-122.16608,{"facility":173,"status":8,"city":174,"state":175,"zip":176,"country":154,"geoPoint":177},"The University of Kansas Medical Center","Westwood","Kansas","66205",{"lat":178,"lon":179},39.04056,-94.6169,{"facility":181,"status":8,"city":182,"state":183,"zip":184,"country":154,"geoPoint":185},"John Hopkins University","Baltimore","Maryland","21205",{"lat":186,"lon":187},39.29038,-76.61219,{"facility":189,"status":8,"city":190,"state":191,"zip":192,"country":154,"geoPoint":193},"Mass General Cancer Center","Boston","Massachusetts","02114",{"lat":194,"lon":195},42.35843,-71.05977,{"facility":197,"status":8,"city":198,"state":199,"zip":200,"country":154,"geoPoint":201},"Karmanos Cancer Institute","Detroit","Michigan","48201",{"lat":202,"lon":203},42.33143,-83.04575,{"facility":205,"status":8,"city":206,"state":206,"zip":207,"country":154,"geoPoint":208},"Columbia University Irving Medical Center","New York","10043",{"lat":209,"lon":210},40.71427,-74.00597,{"facility":212,"status":8,"city":213,"state":214,"zip":215,"country":154,"geoPoint":216},"Sarah Cannon Research Institute Oncology Partners","Nashville","Tennessee","37203",{"lat":217,"lon":218},36.16589,-86.78444,{"facility":220,"status":8,"city":221,"state":222,"zip":223,"country":224,"geoPoint":225},"University Health Network Princess Margaret Cancer Center","Toronto","Ontario","M5G 2C4","Canada",{"lat":226,"lon":227},43.70643,-79.39864,{"facility":229,"status":8,"city":230,"country":231,"geoPoint":232},"Asan Medical Center","Seoul","South Korea",{"lat":233,"lon":234},37.566,126.9784,{"facility":236,"status":8,"city":230,"country":231,"geoPoint":237},"Samsung Medical Center",{"lat":233,"lon":234},{"facility":239,"status":8,"city":230,"country":231,"geoPoint":240},"Seoul National University Hospital",{"lat":233,"lon":234},{"facility":242,"status":8,"city":230,"country":231,"geoPoint":243},"Severance Hospital, Yonsei University Health System",{"lat":233,"lon":234},{"facility":245,"status":8,"city":246,"country":247,"geoPoint":248},"National Taiwan University Hospital","Taipei","Taiwan",{"lat":249,"lon":250},25.05306,121.52639,{"facility":252,"status":8,"city":246,"country":247,"geoPoint":253},"Taipei Veterans General Hospital",{"lat":249,"lon":250},[255],{"name":256,"role":257,"phone":258,"email":259},"Michele Miller","CONTACT","619-728-9693","TyraClinicalTrials@tyra.bio",[261],{"name":262,"affiliation":13,"role":263},"Doug Warner, MD","STUDY_CHAIR",[],[],{"nct_id":4,"conditions":267,"biomarkers":269},[34,268],"Solid Neoplasm",[270,271],"FGF19 Gene","Fibroblast Growth Factor Receptor 3",{"nct_id":4,"found":273,"summary":274,"prompt_version":108},true,{"design":275,"status":276,"heading":277,"summary":278,"follow_up":279,"word_count":280,"commitments":281,"compensation":282,"drugs_mentioned":283},"This is an open-label, multi-center, first-in-human Phase 1 study. It is designed to evaluate TYRA-430 in approximately 100 participants.","completed","TYRA-430 for Advanced Liver Cancer and Other Solid Tumors with FGFR Changes","This study is testing a new drug called TYRA-430 for people with advanced hepatocellular carcinoma (a type of liver cancer) or other solid tumors. To join, your cancer must have specific changes in the FGFR gene. TYRA-430 is given daily by mouth. Researchers want to find the safest dose of TYRA-430 and see how well it works against these cancers. They will also track any side effects you might experience. This is a Phase 1 study, meaning it's one of the first times TYRA-430 is being tested in people. The study aims to enroll about 100 participants.","You would be monitored for side effects from the first dose through 28 days after your last dose of TYRA-430.",97,"Not specified in the trial record.","Not stated in the trial record.",[57]]